Anti-CD19 antibodies inhibit the function of the P-gp pump in multidrug- resistant B lymphoma cells

Maria Ana Ghetie, Victor Ghetie, Ellen S. Vitetta

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

After chemotherapy, tumor cells with multidrug resistance (MDR) often emerge. MDR is attributable to the expression of membrane transport proteins that inhibit the cellular influx and increase the efflux of many chemotherapeutic drugs. One such protein is P-glycoprotein (P-gp), which functions as an ATP-dependent active transporter. Recently, an anti-P-gp monoclonal antibody (MAb) that inhibits P-gp has been described. Previous studies from our laboratory using the anti-CD19 B-cell lymphoma-reactive MAb, HD37, have suggested that HD37 may also influence MDR. To test this directly, we used Namalwa/MDR1 cells to study the effect of HD37 on the efflux of rhodamine 123 from these cells. We found that HD37 and three other anti-CD19 MAbs inhibited the efflux of rhodamine 123 from Namalwa/MDR1 cells with ~50% of the efficiency of the well-known chemosensitizer, verapamil. In contrast, MAbs against seven other molecules expressed on these cells were ineffective. The inhibitory activity of HD37 did not require an Fc portion; F(ab')2 fragments were effective, but Fab' fragments were not, suggesting that higher avidity binding and/or cross-linking of CD19 are necessary. We could find no evidence that HD37 recognizes a cross-reactive epitope on P-gp, modulates P- gp from the cell surface, or enhances the ATPase activity of membranes from treated cells.

Original languageEnglish (US)
Pages (from-to)3920-3927
Number of pages8
JournalClinical Cancer Research
Volume5
Issue number12
StatePublished - Dec 1 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Anti-CD19 antibodies inhibit the function of the P-gp pump in multidrug- resistant B lymphoma cells'. Together they form a unique fingerprint.

  • Cite this